During the administration of anesthesia, anesthesiologists use many sophisticated and expensive devices to monitor the vital signs of and to provide respiratory and cardiovascular support for patients undergoing surgical procedures. Such monitors provide the anesthesiologist with information about the patient's physiologic status and verify that the appropriate concentrations of delivered gases are administered.
Anesthesia can be achieved by using either inhalational or intravenous (IV) anesthetics, or combination of both. Inhalation anesthetics are substances that are brought into the body via the lungs and are distributed with the blood into the different tissues. The main target of inhalation anesthetics (or so-called volatile anesthetics) is the brain. Some commonly used inhalational anesthetics include enflurane, halothane, isoflurane, sevoflurane, desflurane, and nitrous oxide. Older volatile anesthetics include ether, chloroform, and methoxyflurane. Intravenous (IV) anesthetics frequently used clinically are barbiturates, opioids, benzodiazepines, ketamine, etomidate, and propofol. Currently, however, volatile anesthetics are seldom used alone. Rather, a combination of inhalation anesthetics and intravenous drugs are administered, in a process known as “balanced anesthesia.” During administration of balanced anesthesia, for example, opioids are administered for analgesia, along with neuromuscular blockers for relaxation, anesthetic vapors for unconsciousness and benzodiazepines for amnesia.
Inhalational Anesthetics
With inhalation agents, the concentration of drug delivered is metered and the variation between patients in the depth of anesthesia resulting from known concentrations of inhaled agents is relatively narrow, permitting the anesthesiologist to confidently assume a particular level of anesthesia based on the concentration of anesthetic gas delivered.
Monitors used during the administration of inhalational anesthesia generally display inspired and exhaled gas concentrations. Most use side-stream monitoring wherein gas samples are aspirated from the breathing circuit through long tubing lines. A water trap, desiccant and/or filter may be used to remove water vapor and condensation from the sample. Gas samples are aspirated into the monitor at a low rate to minimize the amount of gas removed from the breathing circuit and, therefore, the patient's tidal volume. These gas monitors continuously sample and measure inspired and exhaled (end-tidal) concentrations of respiratory gases. The monitored gases are both the physiologic gases found in the exhaled breath of patients (oxygen, carbon dioxide, and nitrogen), as well as those administered to the patient by the anesthesiologist in order to induce and maintain analgesia and anesthesia.
There are a number of techniques to monitor respiratory gases, including mass spectroscopy, Raman spectroscopy, IR—light spectroscopy, IR—photo acoustics, piezoelectric (U.S. Pat. No. 4,399,686 to Kindlund), resonance, polarography, fuel cell, paramagnetic analysis, and magnetoacoustics. Infrared detector systems seem to be the most commonly used systems to monitor gas concentrations.
A major disadvantage of conventional gas monitors is that they only determine the concentrations of certain types of gases or a limited number of gases and most do not measure N2. These monitors are also fragile, expensive and require frequent calibration and maintenance. For this reason, not all purchasers of anesthesia machines buy anesthesia gas monitors and therefore, rely on anesthesia gas vaporizers to control anesthetic gas concentration. Unfortunately, these vaporizers frequently go out of calibration and the anesthesiologist may administer too much or too little anesthesia.
Intravenous (IV) Anesthetics
Another method of providing anesthesia includes IV anesthetics. At present, a major impediment to the wider use of IV anesthetics, rather than inhaled anesthetics, has been the inability to precisely determine the quantity of drug required to provide a sufficient “depth of anesthesia” without accumulating an excessive amount.
Propofol, for example, is an agent that is widely used as a short acting IV anesthetic. Its physiochemical properties are hydrophobic and volatile. It is usually administered as a constant IV infusion in order to deliver and maintain a specific plasma concentration. Although the metabolism is mainly hepatic and rapid, there is significant interpatient variability in the plasma concentration achieved with a known dose. However, the depth of anesthesia for a known plasma concentration is far less variable and it is therefore highly desirable to be able to evaluate plasma concentrations in real time to accurately maintain anesthetic efficacy. [“A Simple Method for Detecting Plasma Propofol,” Akihiko Fujita, MD, et al., Feb. 25, 2000, International Anesthesia Research Society]. The authors describe a means to measure plasma rather than total propofol using headspace—GC with solid phase microextraction. This is preferable since plasma (free) propofol is responsible for the anesthetic effect. Prior methods of monitoring propofol concentration in blood include high-performance liquid chromatography (HPLC) and gas chromatography (GC). It has been reported that 97%–99% of propofol is bound with albumin and red blood cells after IV injection, and the remainder exists in blood as a free type. HPLC and GC detect the total propofol concentration, which does not correlate as well with the anesthetic effect as the plasma propofol level.
Propofol may also be monitored in urine. Metabolic processes control the clearance of propofol from the body, with the liver being the principal eliminating organ. [“First-pass Uptake and Pulmonary Clearance of Propofol,” Jette Kuipers, et al., Anesthesiology, V91, No.6, December 1999]. In a study, 88% of the dose of propofol was recovered in urine as hydroxylated and conjugated metabolites.
The aim of any dosage regimen in anesthesia is to titrate the delivery rate of a drug to achieve the desired pharmacolgic effect for any individual patient while minimizing the unwanted toxic side effects. Certain drugs such as propofol, afentanil and remifentanil have a close relationship between blood concentration and effect; thus, the administration of the drug can be improved by basing the dosage regimen on the pharmacokinetics of the agent. [Kenny, Gavin, Target-Controlled Infusions—Pharmacokinetics and Pharmodynamic Variations, http://www.anaesthesiologie.med.unierlangen.de/esctaic97/a—Kenny.htm]. Target controlled infusion (TCI) is one means for administering an intravenous anesthesia agent using a computer to control the infusion pump. Using a computer with a pharmacokinetic program permits control of a desired plasma concentration of an agent, such as propofol. The systems do not sample the blood in real-time, but use previously acquired population kinetics to provide a best estimate of the predicted blood concentration. However, even if TCI systems produced the exact target concentrations of blood concentration, it would not be possible to know if that concentration was satisfactory for each individual patient and for different points during the surgical procedure.
Among the technologies used to process and monitor electrical brain signal is BIS (Bispectral Index Monitor) monitoring of the EEG. It is an indirect monitor of depth of anesthesia. The BIS monitor translates EEG waves from the brain into a single number—depicting the depth of anesthesia on a scale from 1 to 100. In addition, neural networks have been used to classify sedation concentration from the power spectrum of the EEG signal. However, this technology is costly and not entirely predictive.
Artificial neural networks have also been developed which use the patient's age, weight, heart rate, respiratory rate, and blood pressure to predict depth of anesthesia. The networks integrate physiological signals and extract meaningful information. Certain systems use mid-latency auditory evoked potentials (MLAEP) which are wavelet transformed and fed into an artificial neural network for classification in determining the anesthesia depth. [Depth of Anesthesia Estimating & Propofol Delivery System, by Johnnie W. Huang, et al., Aug. 1, 1996, http://www.rpi.edu/˜royr/roy—descpt.html].
An apparatus and method for total intravenous anesthesia delivery is also disclosed in U.S. Pat. No. 6,186,977 to Andrews. This patent describes a method in which the patient is monitored using at least one of electrocardiogram (EKG), a blood oxygen monitor, a blood carbon dioxide monitor, inspiration/expiration oxygen, inspiration/expiration carbon dioxide, a blood pressure monitor, a pulse rate monitor, a respiration rate monitor, and a patient temperature monitor.
Combination Inhalational and Intravenous (IV) Anesthetics
As previously stated, anesthesia can be achieved by using either inhalational or intravenous (IV) anesthetics, or combination of both (“balanced anesthesia”). Monitoring techniques for inhalational and intravenous anesthesia differ because of the nature of the drug delivery. Monitors for inhalational anesthesia delivery generally comprise systems that monitor the breathing circuit. Monitors for IV anesthesia generally comprise physiologic monitoring of the patient. Based on this bifurcation of monitoring systems, anesthesiologists must utilize separate systems when switching between drug delivery methods or when utilizing a combination of methods.
Accordingly, there is a need in the art for a monitoring system that determines concentration of both intravenous and inhalational anesthetics, especially during the delivery of “balanced anesthesia.”